3-Hydroxy-3-Methylglutaryl-CoA Synthase Deficiency

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This is rare disorder which is caused by a lack of an enzyme called 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase). This enzyme is needed to produce ketone bodies, which your body needs to provide energy for the brain and other organs during long periods without food or during illness which cause you to refuse food. 

We do not know exactly how common this disorder is. It has been reported in less than 30 people to date. 

Symptoms occur in episodes after long periods without food (fasting) or illness such as gastroenteritis. These episodes are often called crises, and they are often sudden and severe. Symptoms include: 

• Vomiting 
• Lethargy 
• An enlarged liver (hepatomegaly) 
• Low blood sugar (hypoglycaemia) 

If left untreated, crises can progress to cause permanent brain damage, and life-threatening coma. An early diagnosis and correct management of the condition is vital in avoiding these symptoms. 

There are often no symptoms between these crises. 

Due to this disorder having no irregular results on blood and urine tests routinely taken during periods without symptoms, it may be difficult to diagnose. Diagnosis is therefore made with the correct metabolic tests taken during a period of illness or fasting and is confirmed via genetic testing. 

There is no cure for this disorder, it is a lifelong condition. Treatment is based on avoiding long periods without food and. You will be given a special emergency regimen to follow during times of illness which limits or prevents food intake. Your metabolic team will explain this to you in full.  

This disorder can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier. 

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have. 

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene. 

Once you receive a diagnosis, you can speak to a genetic counsellor. They can provide further information about inheritance and can also tell you about genetic testing for the rest of your family. 

References are available on request. Please contact us by phoning 0800 652 3181 or emailing contact@metabolicsupport.org [Resource Library No: HFKB12]. 

Please note calls to 0800 numbers are free from UK landlines and mobiles. Calls from business lines may be charged – please check with your provider.

This information about metabolic diseases is provided by Metabolic Support UK and is intended for educational purposes only. It should not be used for diagnostic or treatment purposes.

Should you require more detailed information please contact Metabolic Support UK by email (contact@metabolicsupport.org) or by telephone ( 0800 652 3181). For specific medical information regarding a disorder or individual please contact your GP or Paediatrician. Metabolic Support UK accepts no responsibility for any errors or omissions nor does Metabolic Support UK assume any liability of any kind for the content of any information contained within this summary or any use that you may make of it.